The avoiding late diagnosis of ovarian cancer (ALDO) project; a pilot national surveillance programme for women with pathogenic germline variants in BRCA1 and BRCA2

• Published in: Journal of medical genetics Vol. 60; no. 5; pp. 440 - 449
• Main Authors: Philpott, Sue, Raikou, Maria, Manchanda, Ranjit, Lockley, Michelle, Singh, Naveena, Scott, Malcolm, Evans, D Gareth, Adlard, Julian, Ahmed, Munaza, Edmondson, Richard, Woodward, Emma Roisin, Lamnisos, Athena, Balega, Janos, Brady, Angela F, Sharma, Aarti, Izatt, Louise, Kulkarni, Anjana, Tripathi, Vishakha, Solomons, Joyce S, Hayes, Kevin, Hanson, Helen, Snape, Katie, Side, Lucy, Skates, Steve, McGuire, Alistair, Rosenthal, Adam N
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01.05.2023; BMJ Publishing Group LTD; BMJ Publishing Group
• Series: Original research
• Subjects: Algorithms; Asymptomatic; BRCA1 protein; BRCA1 Protein - genetics; BRCA2 protein; BRCA2 Protein - genetics; Breast cancer; Cancer Genetics; Coronaviruses; Cost analysis; Cost-Effectiveness Analysis; Costs and Cost Analysis; COVID-19; Delayed Diagnosis; Disease transmission; Early Diagnosis; Economics; Female; Females; Genetic Predisposition to Disease; Genetic Predisposition to Disease - epidemiology; Germ Cells - pathology; Gynecology; Heterozygotes; Humans; Medical referrals; Medical screening; Mutation; Oophorectomy; Ovarian cancer; Ovarian Neoplasms - diagnosis; Ovarian Neoplasms - economics; Ovarian Neoplasms - epidemiology; Ovarian Neoplasms - genetics; Ovariectomy; Pandemics; Population Surveillance; Primary care; Questionnaires; Salpingectomy; State Medicine - economics; Statistical analysis; Surgery; Surveillance; Ultrasonic imaging; United Kingdom - epidemiology; Women's Health; Womens health; United Kingdom; United Kingdom > UK; United States > US; Economics; Genetic Predisposition to Disease; Costs and Cost Analysis; Women's Health; Early Diagnosis
• ISSN: 0022-2593; 1468-6244
• DOI: 10.1136/jmg-2022-108741

BackgroundOur study aimed to establish ‘real-world’ performance and cost-effectiveness of ovarian cancer (OC) surveillance in women with pathogenic germline BRCA1/2 variants who defer risk-reducing bilateral salpingo-oophorectomy (RRSO).MethodsOur study recruited 875 female BRCA1/2-heterozygotes at 13 UK centres and via an online media campaign, with 767 undergoing at least one 4-monthly surveillance test with the Risk of Ovarian Cancer Algorithm (ROCA) test. Surveillance performance was calculated with modelling of occult cancers detected at RRSO. The incremental cost-effectiveness ratio (ICER) was calculated using Markov population cohort simulation.ResultsOur study identified 8 OCs during 1277 women screen years: 2 occult OCs at RRSO (both stage 1a), and 6 screen-detected; 3 of 6 (50%) were ≤stage 3a and 5 of 6 (83%) were completely surgically cytoreduced. Modelled sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for OC were 87.5% (95% CI, 47.3 to 99.7), 99.9% (99.9–100), 75% (34.9–96.8) and 99.9% (99.9–100), respectively. The predicted number of quality-adjusted life years (QALY) gained by surveillance was 0.179 with an ICER cost-saving of -£102,496/QALY.ConclusionOC surveillance for women deferring RRSO in a ‘real-world’ setting is feasible and demonstrates similar performance to research trials; it down-stages OC, leading to a high complete cytoreduction rate and is cost-saving in the UK National Health Service (NHS) setting. While RRSO remains recommended management, ROCA-based surveillance may be considered for female BRCA-heterozygotes who are deferring such surgery.